Overview
Duloxetine is a serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressant used to treat major depressive disorder, generalized anxiety disorder, diabetic peripheral neuropathic pain, fibromyalgia, and chronic musculoskeletal pain. It works by increasing levels of serotonin and norepinephrine in the brain, which helps regulate mood and pain perception.
Mechanism of Action
Duloxetine is a potent dual reuptake inhibitor of serotonin and norepinephrine, increasing neurotransmitter levels in the synaptic cleft. It has minimal affinity for other receptors (dopaminergic, adrenergic, cholinergic, histaminergic, opioid, glutamate, GABA) and does not inhibit monoamine oxidase (MAO).
Indications
- Major depressive disorder in adults
- Generalized anxiety disorder in adults and pediatric patients 7 years and older
- Diabetic peripheral neuropathic pain in adults
- Fibromyalgia in adults and pediatric patients 13 years and older
- Chronic musculoskeletal pain in adults
Common Doses
- 20 mg
- 30 mg
- 60 mg
Dosage
Typically initiated at 30-60 mg once daily, with titration based on indication and tolerability. Maximum recommended dose is 120 mg daily. Should be swallowed whole, not chewed or crushed.
Contraindications
- Concomitant use with MAOIs or within 14 days of discontinuing MAOI therapy
- Starting duloxetine in patients receiving MAOIs like linezolid or intravenous methylene blue
- Known hypersensitivity to duloxetine or capsule components
Side Effects
- Nausea, dry mouth, constipation, diarrhea
- Fatigue, somnolence, insomnia
- Dizziness, headache
- Decreased appetite, weight changes
- Increased sweating
- Sexual dysfunction
- Elevated blood pressure
- Withdrawal symptoms upon discontinuation
Interactions
- MAOIs (contraindicated due to serotonin syndrome risk)
- Other serotonergic drugs (SSRIs, SNRIs, triptans, tramadol)
- CYP1A2 inhibitors (fluvoxamine, ciprofloxacin)
- CYP2D6 inhibitors (paroxetine, fluoxetine)
- Anticoagulants/antiplatelets (increased bleeding risk)
- Drugs affecting blood pressure
Counseling Points
- Take at same time each day, with or without food
- Swallow capsule whole; do not chew, crush, or open
- Avoid abrupt discontinuation; taper under medical supervision
- Report unusual bleeding, bruising, or signs of liver problems
- Monitor for mood changes, especially in first few months
- Use caution when driving or operating machinery until effects known
- Avoid alcohol consumption
- Inform all healthcare providers of duloxetine use before procedures